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Noncommunicable diseases (NCDs) place a huge burden on healthcare systems and society as a whole. Relatively early in the coronavirus disease 2019 (COVID-19) pandemic, clinicians became aware that in individuals infected with COVID-19, those with preexisting NCDs such as diabetes mellitus and cardiovascular disease (CVD) were at a greater risk of poor outcomes and mortality than those without. The importance of adherence to medications and lifestyle changes to control and prevent NCDs has been a major focus for many years, but with limited success – the proportion of patients adherent and persistent to their medications remains very low. There are many facets to adherence and persistence. Recent evidence suggests that a patient-centric approach is important, and ensuring that a patient is both motivated and empowered is critical to improving adherence/persistence. The COVID-19 pandemic has brought many changes to the way in which patients with NCDs are managed, with telemedicine and ehealth becoming more common. Changes have also occurred in the way in which patients can gain access to medications during the pandemic. The potential for these changes forms the basis of improving the management of patients with NCDs both during and after the pandemic. Over the coming months, a huge amount of work will be put into initiatives to promote adherence to COVID-19 vaccination programs. Those at highest risk of severe COVID-19, such as people aged 80 years and older, are likely to receive the vaccine first in some parts of world. Finally, social determinants of health are critical elements that can impact not just the likelihood of having an NCD or becoming infected with COVID-19, but also access to healthcare, and a patient’s adherence and persistence with their treatments.

Noncommunicable diseases (NCDs) are the leading causes of mortality and morbidity across the world and factors influencing global poverty and slowing economic development. We summarize how the potential power of real-world data (RWD) and real-world evidence (RWE) can be harnessed to help address the disease burden of NCDs at global, national, regional and local levels. RWE is essential to understand the epidemiology of NCDs, quantify NCD burdens, assist with the early detection of vulnerable populations at high risk of NCDs by identifying the most influential risk factors, and evaluate the effectiveness and cost-benefits of treatments, programs, and public policies for NCDs. To realize the potential power of RWD and RWE, challenges related to data integration, access, interoperability, standardization of analytical methods, quality control, security, privacy protection, and ethical standards for data use must be addressed. Finally, partnerships between academic centers, governments, pharmaceutical companies, and other stakeholders aimed at improving the utilization of RWE can have a substantial beneficial impact in preventing and managing NCDs.

A vast quantity of real-world data (RWD) are available to healthcare researchers. Such data come from diverse sources such as electronic health records, insurance claims and billing activity, product and disease registries, medical devices used in the home, and applications on mobile devices. The analysis of RWD produces real-world evidence (RWE), which is clinical evidence that provides information about usage and potential benefits or risks of a drug. This review defines and explains RWD, and it also details how regulatory authorities are using RWD and RWE. The main challenges in harnessing RWD include collating and analyzing numerous disparate types or categories of available information including both structured (eg, field entries) and unstructured (eg, doctor notes, discharge summaries, social media posts) data. Although the use of artificial intelligence to capture, amalgamate, standardize, and analyze RWD is still evolving, it has the potential to support the increased use of RWE to improve global health and healthcare.

Objective To generate real‐world evidence (RWE) from the United States to assess the impact of pill burden and the importance of achieving a stable daily dose of sertraline (time taken, number of dose adjustments needed) on adherence/persistence and healthcare resource utilisation (HCRU). Methods Retrospective analysis of the PharMetrics® Plus database (1 October 2012 to 31 March 2020) in the United States. Eligible patients had major depressive disorder (MDD) or obsessive‐compulsive disorder (OCD) and ≥1 claim for sertraline during index period (1 April 2013 to 31 March 2019, allowing 6‐months prior, 1‐year post‐index follow‐up). Patients who achieved stable daily dose of sertraline (>90 days on same dose) were categorised into five cohorts, depending on pill burden/daily dose: Cohort (1): 1 × 50 mg/d; Cohort (2): 1 × 100 mg/d; Cohort (3): 2 × 50 mg/d; Cohort (4): 1.5 × 100 mg/d; Cohort (5): 3 × 50 mg/d. Impact of pill burden on adherence/persistence and HCRU was assessed among cohorts using logistic regression analysis, and between patients who did vs did not stabilise on therapy. P

Since the approval and availability of the first biosimilar in 2015 in the United States (US), evidence regarding the post-marketing safety of cancer supportive care biosimilars remains limited.The aim was to explore the adverse event (AE) reporting patterns and detect disproportionate reporting signals for cancer supportive care biosimilars in the US compared to their originator biologics.The US Food and Drug Administration Adverse Event Reporting System database (January 1, 2004-March 31, 2020) was used to identify AE reports for filgrastim, pegfilgrastim, and epoetin alpha by type of product (originator biologics vs. biosimilars) and report characteristics. Plots of AE reports against years were used to reveal the reporting patterns. Disproportionality analyses using reporting odds ratios (RORs) were conducted to detect differences in serious and specific AEs between studied drugs and all other drugs. Breslow-Day tests were used to determine homogeneity between the originator biologic-biosimilar pair RORs for the same AE.Total numbers of AEs for all studied biosimilars increased after marketing. More AE reports were from female patients for all of the studied drugs. More AEs for originator biologics and filgrastim biosimilar were reported by health professionals, while the highest proportion of reports came from consumers for pegfilgrastim and epoetin alpha biosimilars (29% and 44.1%, respectively). Signals of disproportionate reporting in serious AEs were detected for a pegfilgrastim biosimilar (FulphilaOur findings support the similarity in the signals of disproportionate reporting between cancer supportive care originator biologics and biosimilars, except for Fulphila

Objectives The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil‐P) in 2017 for adult men with erectile dysfunction (ED). A 1‐year prospective real‐world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil‐P. Methods Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil‐P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL‐related outcomes were assessed via the Self‐Esteem and Relationship Questionnaire (SEAR), 2‐Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil‐P use with total physician/nurse practitioner and pharmacist visits and QoL‐related outcomes at 12 months. Results Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate‐to‐severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P

Vaibhav B Katkade, Kafi N Sanders, Kelly H Zou Pfizer Inc, New York, NY, USA Abstract: Evidence from medication use in the real world setting can help to extrapolate and/or augment data obtained in randomized controlled trials and establishes a broad picture of a medication’s place in everyday clinical practice. By supplementing and complementing safety and efficacy data obtained in a narrowly defined (and often optimized) patient population in the clinical trial setting, real world evidence (RWE) may provide stakeholders with valuable information about the safety and effectiveness of a medication in large, heterogeneous populations. RWE is emerging as a credible information source; however, there is scope for enhancements to real world data (RWD) sources by understanding their complexities and applying the most appropriate analytical tools in order to extract relevant information. In addition to providing information for clinicians, RWE has the potential to meet the burden of evidence for regulatory considerations and may be used in approval of new indications for medications. Further understanding of RWD collection and analysis is needed if RWE is to achieve its full potential. Keywords: electronic health records, evidence-based medicine, real world data, real world evidence, randomized controlled trial

Aims Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. Methods MEDLINE®, Embase®, and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as “elderly”). To assess study quality of RCT reports, we focused on internal/external validity, assessed via two scales: the validated Effective Public Health Practice Project [EPHPP]): Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the Agency for Healthcare Research and Quality (AHRQ). Results Database searches yielded 1380 records that were then screened according to predefined inclusion/exclusion criteria. We included eight papers meeting study criteria. Despite scientific community efforts to improve RCT reporting standards, published reports still include incomplete and inconsistent reporting—of subject attrition, baseline patient characteristics, inclusion/exclusion criteria, and other important details. Only three of the eight OAB RCTs in this review received quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large samples. Conclusions Despite the prevalence of OAB among older age individuals, relatively few RCTs evaluate OAB treatments explicitly among elderly subjects. The findings from this quality assessment suggest some areas for improvement in both conduct and reporting of future RCTs assessing OAB treatment in elderly.

Months of conference planning can take mere minutes with a dash of optimisation. By Jason Pan, Kelly H. Zou, Ching-Ray Yu, Franklin W. Sun, and Martin O. Carlsson

Aims Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are highly prevalent conditions that place a large burden on the United States (US) health care system. We sought to analyze patterns of prescription medication usage for incident OAB in men and women, and for incident BPH in men using US health insurance claims data. Materials and Methods This study used Truven Health MarketScan® Commercial and Medicare Supplemental Research databases. The data were pooled from diverse points of care. BPH subjects included men age 18+ with the first and last two diagnoses of BPH ≥30 days apart and no BPH diagnosis for 1 year prior. OAB subjects included men and women age 18+, who were diagnosed similarly with incident OAB. The type of medication, medication continuation (persistence), and switching to a different medication were analyzed through September 30, 2013. Results Medication persistence was much higher overall for BPH than OAB (56% vs 34%, respectively, P

Smoking is the leading preventable cause of death, and tobacco control professionals continue to make progress in cessation efforts. Pharmacists can assist smokers seeking to quit by offering counseling on smoking cessation pharmacotherapies. Pragmatic randomized trials are useful for investigating practical questions about an intervention's risks, benefits, and costs in routine clinical practice.To evaluate an enhanced pharmacy care (EPC) program involving personalized pharmacist-provided telephone counseling for supporting prescription smoking cessation medications compared with usual care (UC).Cigarette smokers filling a newly prescribed smoking cessation pharmacotherapy and with pharmacy benefits managed by Express Scripts were recruited. Qualified subjects were randomized 1:1 to EPC and UC. Subjects in EPC received 3 telephone-counseling sessions from specialist pharmacists during the early course of the study, while subjects in UC did not receive any counseling sessions. Study outcomes were collected through telephone contact and using the Express Scripts prescription database. The primary outcome assessed the 1-week point prevalence (PP) of smoking abstinence at the end of the trial (week 12). Secondary outcomes included 4-week PP at week 12 and adherence, evaluated by proportion of days covered (PDC), to prescribed smoking cessation pharmacotherapies.There were 1,017 randomized subjects. Among them, 1,002 subjects were included in the analysis, and 513 were randomized into EPC and 489 into UC. Baseline demographics, smoking history, and prescribed smoking cessation pharmacotherapies were comparable. Varenicline and nicotine replacement therapy (NRT) were most frequently prescribed for smoking cessation. In EPC, 46.0% received all 3 counseling sessions; 29.4% received 2 sessions; and 14.6% received 1 session. Overall, 353 subjects in EPC and 383 subjects in UC completed the week 12 assessment. In the analysis for 1-week PP of smoking abstinence at week 12, the percentage of abstainers in EPC was numerically higher than in UC (42.3% vs. 38.2%) with OR = 1.24, 95% CI = 0.96-1.61. It was not statistically significant. Adherence to prescription smoking cessation medication was significantly higher in EPC versus UC (49.7% vs. 45.6%; P = 0.033).This study evaluated whether a telephone-based pharmacy care program, provided by pharmacists and designed to support attempted quitters, improved quitting and increased adherence over usual care. The findings suggest that an enhanced program may benefit smokers by increasing prescription smoking cessation medication adherence. Future research should explore this program's effect on smokers who are compliant, based on insights on quitting provided by the post hoc analyses and limitations of the current study design.This study was sponsored by Pfizer. Gong, Baker, Zou, Bruno, Jumadilova, and Lawrence are employees and stockholders of Pfizer. Wilson and Ewel are employees of United BioSource Corporation, which received funding from Pfizer for conducting this study and for the development of this manuscript. Study concept and design were contributed by Gong, Bruno, and Ewel, with assistance from Jumadilova, Lawrence, and Zou. Gong, Jumadilova, Lawrence, and Ewel collected the data. Data interpretation was performed by Baker, Zou, and Wilson, assisted by Gong, Lawrence, and Ewel. The manuscript was written by Baker, Ewel, and Gong, with assistance from the other authors, and revised by Baker, Wilson, Zou, and Gong, with assistance from Bruno and Jumadilova.

SummaryAims With self-reporting of erectile dysfunction (ED) in population-based surveys, men with ED may not represent men who are bothered sufficiently to seek an ED diagnosis and treatment. We used real-world observational data to assess: 1) the prevalence of ED diagnosis or treatment by age subgroups; and 2) the relationship of age with ED diagnosis or treatment after controlling for ED-related comorbidities in the USA. Methods This cross-sectional study used de-identified claims data (MarketScan® databases; primary analysis). Sensitivity analysis was conducted using electronic health records (Humedica® database). Inclusion criteria were men aged ≥18 years with a 360-day continuous enrollment before the index date. We assessed the prevalence of ED diagnosis or phosphodiesterase type 5 inhibitor (PDE5I) prescription by age and the risk for ED diagnosis or treatment by age after controlling for comorbidities (hypertension, other cardiovascular disease, diabetes mellitus, depression and benign prostatic hyperplasia). Results Of 19,833,939 men meeting inclusion criteria in the primary analysis, only 1 108 842 (5.6%) had an ED diagnosis or PDE5I prescription (mean [SD] age: 55.2 [11.2] years). Prevalence of ED diagnosis or treatment increased from age 18–29 years (0.4%) to 60–69 years (11.5%), then decreased in the seventh (11.0%), eighth (4.6%), and ninth (0.9%) decades. Men with ED diagnosis or treatment had a higher prevalence of any comorbidity (63.1% vs 29.3% for men without ED) and of each comorbid condition. In multivariate analyses, age was an independent risk factor for ED diagnosis or treatment. Sensitivity analysis provided consistent results. Conclusions In a real-world setting in the USA, the prevalence of ED diagnosis or PDE5I treatment is generally low, increases with age, decreases in very old men, and is associated with increased prevalence of comorbidities. Age is an independent risk factor for ED diagnosis or treatment after controlling for comorbidities.

Objective To examine the “real-world” overactive bladder (OAB) practice patterns using national data in the United States. Materials and Methods The Humedica EHR database was queried. This database consists of de-identified patient records from a network of organizations treating approximately over 30 million patients across states in the United States. The entire study period was from July 1, 2008, to September 30, 2013. Patients with a diagnosis of OAB between July 1, 2009, and June 30, 2012 were included and followed. Patient comorbidities, demographics, diagnostic testing, and medication usage were analyzed. Results Of 19,309,600 subjects enrolled during the study period, 46,648 adults had a diagnosis of OAB, with follow-up of at least 6 months, and met the inclusion criteria. There were 35,315 women and 11,333 men. Compared with women, men with OAB were more likely to undergo post-void residual measurement (32% vs 22%) and diagnostic cystoscopy (10% vs 7%). Women were more likely than men to undergo urodynamics (7% vs 3%). Overall, 34% of women and 19% of men diagnosed with OAB were prescribed medication. Conclusion Few patients with OAB underwent invasive diagnostic testing. Anticholinergic medication was prescribed to a minority of patients diagnosed with OAB, indicating possible underuse of a potentially effective therapy. Men were less likely than women to receive medical therapy, despite the fact that OAB is common in both sexes.

Summary Objectives This study examined potential benefits of diagnosing and treating elderly adults with overactive bladder (OAB) symptoms. Methods Data were analysed from the OAB Re-Contact Study (N = 2750), a cross-sectional, self-reported Internet survey. Elderly respondents (65+ years old) with OAB were identified according to current medication use to control OAB symptoms or by scores > 14 (men) or > 16 (women) on the OAB Awareness Tool. Treated were those currently using prescription medication and never treated were those who never used prescription medication for OAB. Outcome measures included health-related quality of life, activity impairment, OAB-related severity and symptoms, and healthcare resource use (e.g. hospitalisations). Generalised linear models predicted health outcomes as a function of diagnosis or treatment, adjusting for covariates. Results Diagnosed vs. not diagnosed elderly respondents had higher mental component summary (MCS) scores and SF-6D health utilities, and less activity impairment. Treated vs. never treated elderly respondents had higher MCS and SF-6D health utilities, less activity impairment, fewer OAB symptoms, lower OAB Awareness Tool scores, and lower odds of having bladder problems or incontinence. There were no significant differences in healthcare resource use. Further analysis by age group (middle-aged vs. elderly respondents) revealed significantly greater diagnosis- and treatment-related benefits on MCS (2.93 and 4.49 points more, respectively) and activity impairment (1.24 and 1.37 times as much, respectively) among elderly respondents. Conclusions Diagnosis and treatment were each associated with a lower health burden for elderly adults with OAB symptoms. These findings highlighted the importance of diagnosis and treatment in alleviating OAB symptoms and their impact on health outcomes.

The purpose of this study was to assess the effectiveness and safety of air versus liquid enema reduction in the treatment of intussusception in children.Literature searches of the PubMed, Embase, and Cochrane Library databases were conducted from January 1, 1966, through May 31, 2013. Articles on the use of air or liquid enema in children with a confirmed diagnosis of intussusception and reporting either a success rate for enema reduction of intussusception or a perforation rate were selected. Enema reduction success rate, perforation rate, and recurrence rate were the main outcomes and were calculated by random effects modeling.One hundred two articles (101 reporting success rate, 71 reporting perforation rate) were included that presented results for 32,451 children (age range, 1 day-22 years; boys, 66%; girls, 34%). In 44 studies (16,187 children), the combined estimate for success rate of air enema was 82.7% (95% CI, 79.9-85.6%; inconsistency index [I(2)] = 97%), and in 52 studies (13,081 children) of liquid enema, it was 69.6% (95% CI, 65.0-74.1%; I(2) = 98%). In 38 studies (15,752 children), the combined estimate of perforation rate for air enema was 0.39% (95% CI, 0.23- 0.55%; I(2) = 40%), and in 30 studies (9429 children) of liquid enema, it was 0.43% (95% CI, 0.24- 0.62%; I(2) = 9%). Among 10,494 children (26 studies) undergoing air enema reduction, the rate of first intussusception recurrence was 6% (95% CI, 4.5-7.5%; I(2) = 89%), similar to the 7.3% (95% CI, 5.8-8.8%; I(2) = 71%) found for 4004 children (24 studies) undergoing liquid enema reduction.Air enema was superior to liquid enema for intussusception reduction. The success rate was higher without a difference in perforation rate. Limitations included heterogeneity and publication bias.

This chapter presents best practices and guidelines for conducting and reporting data from health economics and outcomes research. A brief summary of different data source types and study design methodologies is provided in the final chapter of the book. It is noted that research findings based on these outcomes should be interpreted with caution in order to support claims that are consistent with medical product labels. Several guidance resources are highlighted, including those from the International Society for Pharmacoeconomics and Outcomes Research, and other professional and governmental bodies.

Summary Objectives To assess the prevalence, patient–physician communication, treatment and health outcomes associated with urinary incontinence (UI) among the medically complex vulnerable elderly (MCVE) in the United States (US). Methods Data from the 2006 to 2012 Medicare Health Outcomes Survey (HOS) were used. MCVE patients were aged 65+ years with a HOS VE score ≥ 3. UI was reported as a small, big or no problem. Descriptive statistics were used to assess patient–physician communication and treatment. Multivariable regression analyses were performed to assess the association of small or big UI problems with various outcomes. Results The annual UI prevalence increased among MCVE [from 35.8% (2006) to 38.6% (2012)]. MCVE with big UI problems communicated with their physicians more often than those with small UI problems (77.9% and 49.6%, respectively); however, treatment of UI remained low (48.5% and 29.1%, respectively). Physical component summary (PCS) and mental component summary (MCS) scores were lower among MCVE with small or big UI problems compared with those with no UI problems, respectively. The decrements in PCS and MCS scores associated with big UI problems were greater than the decrements associated with any of the other assessed conditions. MCVE with small or big UI problems, respectively, were more likely to report past falls, depression and activity daily living limitations vs. those without UI. The odds of having experienced these outcomes were greater for those with big UI vs. small UI problems. Conclusions Urinary incontinence prevalence in the USA increased among MCVE from 2006 to 2012, although treatment of UI remained low. UI problems, particularly big UI problems, adversely impact health outcomes. Efforts to better identify and manage UI among the MCVE are needed.

Overactive bladder (OAB) and related conditions, such as urge urinary incontinence (UI), can interfere with work, leisure activities, and healthy sleep patterns.To report (a) employee urinary antispasmodic (UA) medication persistence and adherence; (b) the impact of salary and copay on adherence; and (c) the impact of UA adherence on medical, pharmacy, sick leave (SL), short- and long-term disability (STD, LTD), workers' compensation costs, work absence days, and turnover.This retrospective study used a 2001-2011 database of claims, payroll, and demographic data from 27 large U.S. employers. Employees aged 18-64 years taking UA medications with health plan enrollment from 6 months before the index UA medication prescription to 12 months after were included. Persistence (days until first ≥ 30-day gap in UA medication supply) and adherence (percentage of the annual post-index period with available medication) were assessed using survival analysis and generalized linear regression models that controlled for demographics, job-related factors, copay, and pre-index employee benefit utilization. 2,960 employees met study criteria. Median days of persistence by OAB subtype were 76, 82, 43, 66, and 60 for urge UI, mixed UI, nocturnal UI, other OAB, and no diagnosis, respectively (P less than 0.05 for urge and mixed vs. no diagnosis). Increased copay and copay as a percentage of salary were associated with lower adherence. Employees with ≥ 80% adherence had lower medical, SL, and STD and higher overall drug costs than employees with less than 80% adherence. This study suggests potential economic benefits to employers from increased UA adherence. Additionally, economic factors such as ability to pay influence adherence to UA medications.

SummaryBackground Smoking has important health and economic consequences for individuals and society. This study expands the understanding of work-related burden associated with smoking and benefit of smoking cessation across the US, European Union (EU) and China using large-scale, representative survey methodology. Methods Data utilised the 2013 National Health and Wellness Survey in United States (US), EU5 (UK, France, Germany, Italy, and Spain) and China. Working-aged respondents 18-64 were used in the analyses (US N=58 500; EU5 N=50 417; China N=17 987) and were categorised into: current smokers, trying to quit, former smokers and never smokers. Generalised linear models controlling for demographics and health characteristics examined the relationship of smoking status with work productivity and activity impairment (WPAI-GH). The WPAI-GH measures were: absenteeism, presenteeism, overall work impairment, and activity impairment. Separately, current smokers were compared with those who quit 0-4, 5-10 and 11 or more years ago on WPAI-GH end-points. Results Current smokers reported greater absenteeism in the US and China and greater presenteeism, overall work impairment, and activity impairment than former and never smokers across the three regions. Those who quit even 0-4 years ago demonstrated lower absenteeism, presenteeism, and activity impairment in China and lower presenteeism, overall work impairment, and activity impairment in the US and EU5. Conclusions Smoking was associated with significant work productivity loss in the US, EU5 and China. The results suggest that quitting benefits extend to work productivity rapidly after cessation, serving to further encourage and promote the implementation of workplace cessation programs.

Background: Varenicline is a smoking cessation medication. Objectives: We analyzed patients’ out-of-pocket costs and utilization of and persistence with varenicline. Methods: De-identified claims data in the MarketScan® Commercial Claims and Encounters Database were analyzed retrospectively. Participants were all patients at least 18 years of age continuously enrolled in plans during 2009. Plans were categorized according to restriction (no coverage; prior authorization; smoking cessation program requirement; no restrictions) and out-of-pocket cost for a 30-day supply (low

Adherence with oral medication for overactive bladder syndrome is suboptimal. To improve adherence, the YourWay plan was developed to assist patients and health care providers in defining treatment expectations and facilitating communication.To evaluate medication adherence among patients with overactive bladder syndrome enrolled in the YourWay patient support plan, patient adoption of behavioral interventions, patient satisfaction with the plan, and physician experience with the plan.In this 13-week, single-arm, open-label, multicenter, noninterventional study, fesoterodine-naïve patients received a prescription for fesoterodine 4 or 8 mg and a packet including a 14-day fesoterodine sample, educational materials, and progress tracker. Patients registered for the YourWay plan, which included an educational resource kit, interactive voice-response calls, and optional online and mail support. The primary end point was the proportion of patients who filled a prescription for a ≥ 90-day supply of fesoterodine within 90 days of enrollment. Secondary end points were the proportion of patients who filled ≥ 1 prescription and ≥ 2 prescriptions (post hoc), patient evaluation of their experience and satisfaction with the YourWay plan, and differences between prescription fillers and nonfillers in plan adoption and assessment (post hoc). We surveyed an independent sample of physicians to assess their experience with YourWay.Of 500 study completers, 10.4% filled a prescription for a ≥ 90-day supply of fesoterodine. Of those filling a prescription, 26.2% filled ≥ 1 prescription and among those, 61.0% refilled their prescription at least once. Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers were more likely to take fesoterodine as directed, whereas adoption of behavioral recommendations or plan satisfaction did not differ between fillers and nonfillers. Most patients reported that the plan was informative and feasible to implement, and that they were satisfied with various aspects of the plan. Physicians also reported positive experiences.Most patients adopted YourWay components and viewed the plan positively, although adherence remained a challenge.

OBJECTIVE Quantify incremental employee medical, pharmacy, sick leave, short- and long-term disability, and workers' compensation costs, absence days, and turnover associated with urge urinary incontinence (UUI) in employees. METHODS This retrospective 2001-2011 database comparison of employees with UUI versus those without UUI (controls) included employees aged 18.5 to 64.0 years at index, with 6-month preindex and 12-month postindex health plan enrollment. Logistic and generalized linear models measured postindex costs, absences, and turnover. RESULTS The study included 1448 employees with UUI and 337,796 controls. Employees with UUI had statistically significantly higher medical (131% higher), pharmacy (52%), sick leave (30%), and short-term disability (74%) costs and more sick leave (22%) and short-term disability (99%) days than controls (all P < 0.02). CONCLUSIONS Employees with UUI had 117% greater medical and pharmacy costs, 47% greater total absence costs, and 63% more absence days than employees without UUI.

Summary Objective To evaluate the impact of treating urge urinary incontinence (UUI), including mixed urinary incontinence (MUI), on healthcare resource utilisation, productivity, activity impairment and associated costs. Methods The study used data from the 2011 U.S. National Health and Wellness Survey, an Internet-based questionnaire of a nationwide sample of adults. UUI or MUI respondents were identified via three Incontinence Questions. Respondents with stress urinary incontinence only, prostate cancer or (medication for) benign prostatic hyperplasia were excluded. UUI/MUI respondents were categorised as Rx users for overactive bladder (OAB) and non-Rx users (who never used Rx and whose condition reportedly interfered with life activities or was difficult to manage). Outcome measures included healthcare utilisation and Work Productivity and Activity Impairment questionnaire-based scores. Direct and indirect costs were estimated using 2010 labour and 2008 medical expenditure data sources. Generalised linear models predicted resource use and productivity as a function of treatment status, adjusting for covariates (e.g. sociodemographics, OAB severity, comorbid status) that may also predict impairment. Results Rx (vs. non-Rx) users were more likely to be female (80.7% vs. 70.0%), older (mean = 62.7 vs. 53.1) and reporting more moderate-to-severe OAB (70.9% vs. 52.6%; all p

To assess the impact of access restrictions on varenicline utilization.Employer-sponsored health plans contributing to the MarketScan Commercial Claims and Encounters Database were categorized according to 2009 varenicline access restrictions: no coverage; prior authorization; smoking cessation program requirement; no restrictions. The cohort comprised all adults continuously enrolled in plans during 2009. Each restriction cohort was compared with the no restrictions cohort using descriptive analyses. Data were assessed using logistic regression; demographic and clinical characteristics were covariates.In this study (no coverage, n = 454,419; prior authorization, n = 171,530; smoking cessation program, n = 108,181; no restrictions, n = 607,389), compared with the no restrictions cohort, the odds of treatment were 71% lower (odds ratio: 0.29; 95% CI: 0.26, 0.31) in the smoking cessation program cohort (p0.001) and 80% lower (odds ratio: 0.20; 95% CI: 0.19, 0.22) in the prior authorization cohort (p0.001).Access restrictions were associated with significantly lower odds for varenicline utilization.

INTRODUCTION Concerns exist that varenicline may cause neuropsychiatric side effects. Some of these symptoms (e.g., depression, irritability) have been measured in clinical trials using nicotine withdrawal scales. This study assessed the effect of varenicline on neuropsychiatric and other symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). METHODS We analyzed weekly individual MNWS symptom ratings in 8 randomized double-blind, placebo-controlled smoking cessation trials funded by Pfizer with similar methodology (n = 2,403 varenicline; n = 1,434 placebo). Ratings for the past 24hr were obtained prior to quitting and starting treatment and at Weeks 1-6 and 11 after the quit date. RESULTS In repeated measures analyses controlling for baseline values, ratings for 5 neuropsychiatric symptoms (depressed mood, irritability, anxiety, difficulty concentrating, and restlessness) and urge to smoke were lower (p < .01) for varenicline than placebo at each timepoint. Worsening in scores from 0-2 (baseline) to 4 was less frequent on varenicline than placebo for all ratings except appetite- (significantly more frequent for varenicline, p < .0001) and sleep-related items. Repeated measures analysis for individuals with low levels of exhaled carbon monoxide revealed similar patterns except for a nonsignificant difference for increased appetite. CONCLUSIONS Use of varenicline while trying to quit smoking reduces and does not increase neuropsychiatric symptoms such as depressed mood and irritability measured on the MNWS in smokers without current psychiatric disorders. It is associated with increases in sleep disturbance and appetite although the latter appears due to enabling more subjects to abstain from smoking.

BACKGROUND: Varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, is a pharmacotherapy indicated for smoking cessation treatment. To our knowledge, no studies have described varenicline treatment adherence and efficacy from real-world treatment patterns in a U.S. primary care setting. OBJECTIVE: To estimate adherence to varenicline prescription orders and subsequent quit rates among smokers in a primary care setting. METHODS: In this retrospective cohort study, eligible patients were enrolled with Geisinger Health Plan, had an initial varenicline prescription written by a Geisinger provider between January 1, 2006, and December 31, 2009, and had a follow-up clinic visit within the subsequent 12 months. Adherence was derived from linking electronic prescriptions with adjudicated pharmacy claims. Smoking status was collected at each health care encounter. RESULTS: Of the 1,477 eligible patients, 823 (55.7%) were primary nonadherent, having failed to initiate on the prescribed varenicline therapy. Of the remaining 654 patients, 359 (54.9%) were adherent, having completed a full 12-week course of therapy, and 295 (45.1%) were partially adherent, having initiated but not completed the full course of therapy. A total of 521 patients (35.3%) ceased smoking during the 12-month follow-up period: 182 (50.7%) of the adherent cohort, 82 (27.8%) of the partially adherent population, and 257 (31.2%) of the nonadherent cohort. No significant difference was found in quit rates between the partially adherent and nonadherent patient cohorts (adjusted HR 0.88 [95% CI = 0.69-1.13]). However, patients adherent to the varenicline regimen were almost twice as likely to succeed in quitting smoking compared with completely nonadherent patients (HR 1.93 [95% CI = 1.59-2.33]). CONCLUSION: Smoking cessation occurred more often among individuals adherent to varenicline therapy; however, medication nonadherence was common. After prescribing varenicline, clinicians and payers could consider active patient follow-up to maximize adherence and optimize treatment outcomes.

With the growing focus on comparative effectiveness research and personalized medicine, receiver-operating characteristic analysis can continue to play an important role in health care decision making. Specific applications of receiver-operating characteristic analysis include predictive model assessment and validation, biomarker diagnostics, responder analysis in patient-reported outcomes, and comparison of alternative treatment options. The authors present a survey of the potential applications of the method and briefly review several relevant extensions. Given the level of attention paid to biomarker validation, personalized medicine and comparative effectiveness research, it is highly likely that the receiver-operating characteristic analysis will remain an important visual and analytic tool for medical research and evidence-based medicine in the foreseeable future.

Objectives: Although much has been published about the demographic and clinical characteristics of elderly patients with overactive bladder (OAB) who were enrolled in clinical trials, very little is known about the general population of elderly Americans with OAB. We update this gap in the literature by using real-world data to describe this population. Methods: We used Medicare claims and the Medicare Current Beneficiary Surveys from 2006 to 2011 to identify patients with OAB. We describe the demographic characteristics, functional impairment and physical limitations, concurrent medical conditions, Charlson Comorbidity Index (CCI) scores, and concomitant medication use of patients with OAB; these characteristics are also described by sex and age group (65–74 vs. ≥75 years). We also compare the characteristics of OAB with non-OAB patients. Results: We identified 415 elderly patients with OAB (average age 79 years; 71% female) and 6868 without OAB (average age 77 years; 62% female). Patients with OAB reported high levels of functional impairment as measured by the Activities of Daily Living (44% vs. 33% for non-OAB patients), Instrumental ADL (53% vs. 40% for non-OAB patients), and physical functioning limitation (90% vs. 81% for non-OAB patients) scales. Elderly patients with OAB also experienced high levels of comorbidity burden, as measured by the number of medical conditions (18 vs. 11 for non-OAB patients), CCI (2.1 vs. 1.4 for non-OAB patients), and number of non-OAB-related concomitant medications used (11 vs. 8 for non-OAB patients). Conclusions: Elderly patients with OAB in the general population have high levels of functional impairment and physical limitations, comorbidity, and concomitant medication use. These characteristics should be taken into consideration when managing OAB symptoms and designing future clinical studies. These results, which are representative of elderly patients with OAB in the general US population, should, however, be interpreted in light of the key limitations of the data we used: patients may have been misclassified and medical conditions overestimated due to artifacts of diagnosis coding and our results can only be generalized to patients who were enrolled in Medicare Parts A, B, and D for at least 12 continuous months.

What's known on the subject? and What does the study add? Studies on erectile dysfunction (ED) therapies rely heavily on patient-reported outcomes (PROs) to measure efficacy on treatment response. A challenge when using PROs is interpretation of the clinical meaning of changes in scores. A responder analysis provides a threshold score to indicate whether a change in score qualifies a patient as a responder. However, a major consideration with responder analysis is the sometimes arbitrary nature of defining the threshold for a response. By contrast, cumulative response curves (CRCs) display patient response rates over a continuum of possible thresholds, thus eliminating problems with a rigid threshold definition, allowing for a variety of response thresholds to be examined simultaneously, and encompassing all data. With respect to the psychosocial factors addressed in the Self-Esteem And Relationship questionnaire in ED, CRCs clearly, distinctly, and meaningfully highlighted the favourable profiles of responses to sildenafil compared with placebo. CRCs for PROs in urology can provide a clear, transparent and meaningful visual depiction of efficacy data that can supplement and complement other analyses. OBJECTIVE • To use cumulative response curves (CRCs) to enrich meaning and enhance interpretation of scores on the Self-Esteem And Relationship (SEAR) questionnaire with respect to treatment differences for men with erectile dysfunction (ED). PATIENTS AND METHODS • This post hoc analysis used data from all patients who took at least one dose of study drug and had at least one post-baseline efficacy evaluation in a previously published 12-week, multicentre, randomized, double-blind, placebo-controlled trial of flexible-dose (25, 50, or 100 mg) sildenafil citrate (Viagra) in adult men with ED who had scored ≤ 75 out of 100 on the Self-Esteem subscale of the SEAR questionnaire. • CRCs were used on the numeric change in transformed SEAR scores from baseline to end-of-study for each SEAR component. • The horizontal axis of the CRC represented change from baseline on the SEAR score, and the vertical axis represented the percentage of patients experiencing that change or greater. • The differences between CRCs for the sildenafil group vs the placebo group were assessed using the Kolmogorov–Smirov test. RESULTS • For each of the SEAR components, there was essentially no overlap in the CRCs between the sildenafil group (n= 113) and placebo group (n= 115 or 116, depending on the component), showing that a greater percentage of sildenafil recipients compared with placebo recipients had a more favourable change across the spectrum of response thresholds (P≤ 0.01). • Previous research showed that a 10-point score increase is the minimal clinically meaningful improvement for most SEAR components. In the sildenafil vs placebo groups, a ≥10-point score increase occurred in 72 vs 37% of patients, respectively, on the Sexual Relationship Satisfaction domain, 71 vs 41% on the Confidence domain, 76 vs 49% on the Self-Esteem subscale, 60 vs 44% on the Overall Relationship Satisfaction subscale, and 75 vs 38% on the Overall score. CONCLUSIONS • With respect to the psychosocial factors addressed in the SEAR questionnaire, CRCs clearly, distinctly, and meaningfully highlighted the favourable profiles of responses to sildenafil compared with placebo. • CRCs for patient-reported outcomes in urology can provide a clear, transparent, and meaningful visual depiction of efficacy data that can supplement and complement other analyses.

Small-vessel disease is a common MRI finding that can be difficult to differentiate from other white matter (WM) diseases because of the lack of a specific pattern of brain involvement. The purpose of our study was to evaluate medial lemniscus hyperintensity seen on FLAIR images as an imaging marker for small-vessel disease.Two blinded neuroradiologists retrospectively reviewed 103 consecutive outpatient brain MRI studies. Medial lemniscus signal in the dorsal pons was evaluated visually on FLAIR images and after placing regions of interest (ROIs) on T2-weighted images. On the basis of the original interpretations, scans were divided into three categories: small-vessel disease, multiple sclerosis (MS), and normal or nonspecific WM changes. Cardiovascular risk factors were recorded. Analysis of variance and Fisher exact tests were used to determine group differences, and kappa statistics was used to determine interrater agreement.Thirty-seven patients had small-vessel disease, 14 patients had MS, and 52 had nonspecific WM changes. Medial lemniscus hyperintensity was seen in about 20% of patients with small-vessel disease and was generally bilateral. Although ROI analyses identified a slightly higher number of patients with medial lemniscus signal20% of adjacent to normal-appearing brainstem, interrater reliability was moderate, and there were false-positive and false-negative cases in comparison with visual data. When small-vessel disease patients were further subdivided into mild or advanced subgroups, medial lemniscus hyperintensity was selectively seen in advanced small-vessel disease. Patients with medial lemniscus hyperintensity were older (p0.001) and had higher prevalence of diabetes (p = 0.03), hypertension (p = 0.009), and hypercholesterolemia (p = 0.03).Medial lemniscus hyperintensity seen on FLAIR images is a reliable radiologic marker of advanced small-vessel disease.

To address the gap in knowledge about the impact of chronic obstructive pulmonary disease (COPD) on older working adults, this study examined quality of life, worker productivity, and healthcare resource utilization among employed adults aged 65 and older with and without COPD. Among 2009 National Health and Wellness Survey (a cross-sectional, internet-based survey representative of the US adult population) respondents, employed adults aged 65 years and older, with COPD (n = 297) and without COPD (n = 3061), were included in analyses. Impact of self-reported COPD diagnosis on mean quality of life (using health utilities and mental, MCS, and physical, PCS, component summary scores from SF-12v2), work productivity and activity impairment (using the WPAI questionnaire), and resource use were examined. Adjusting for demographic and health characteristics such as co-morbidities (weighted to project to the US population) in regression models (linear, negative binomial, or logistic, as appropriate given the outcome measure), older workers with COPD reported significantly lower MCS (52.1 vs. 53.4, p < .05), PCS (40.3 vs. 47.2, p < .05), and health utilities (0.72 vs. 0.79, p < .05) than those without COPD, and significantly greater percentages of impairment while at work (presenteeism) (12.6% vs. 8.7%, p < .0001), overall work impairment (absenteeism and presenteeism combined) (19.3% vs. 10.0%, p < .05), and impairment in daily activities (23.9% vs. 13.7%, p < .05). There were no significant differences in absenteeism or healthcare use. Quality of life and work productivity suffered among employed adults aged 65 years and older with COPD, emphasizing the need for disease management in this population.

We examined diagnostic tests and treatment patterns in men with new onset benign prostatic hyperplasia using consolidated national electronic health record data.The Humedica® electronic health record database consists of de-identified patient records from approximately 25 million patients in the United States. Using this database, men with a new benign prostatic hyperplasia diagnosis (benign prostatic hyperplasia, bladder neck obstruction, urinary retention and incomplete bladder emptying) between July 1, 2009 and June 30, 2012 were included in study. Exclusion criteria included conditions such as genitourinary cancers, radiation cystitis, neurogenic bladder and urological pain diagnoses. Diagnostic tests and treatments were summarized and stratified by age (less than 65 vs 65 years or greater) and serum prostate specific antigen level.A total of 38,252 men met inclusion criteria. Mean followup was 1,020 days. Serum creatinine in 92% of patients, serum prostate specific antigen in 76% and urinalysis in 52% were the most common tests. Invasive testing was obtained in less than 20% of patients. Treatments included watchful waiting in 40% of patients, pharmacological therapy in 59.4% and surgery in 2.2%. α-Blockers were prescribed in 50.7% of men. Men older than 65 years and with higher prostate specific antigen levels were less likely to be treated with watchful waiting. Therapy with a 5-ARI (5-α reductase inhibitor) was prescribed in 23% to 29% of men across all prostate specific antigen categories.The majority of clinical care for new onset benign prostatic hyperplasia was in concordance with guideline recommendations. Based on prostate specific antigen values, 5-ARI therapy was underutilized in men with large prostates and was over utilized in men with small prostates.

To assess the costs of treating overactive bladder (OAB) with fesoterodine compared to no OAB pharmacotherapy among vulnerable elderly from the US payer perspective.A decision analytic cost model was developed to estimate the 52-week costs of a cohort of vulnerable elderly with OAB initiating treatment with fesoterodine or no OAB pharmacotherapy. Vulnerable elderly OAB patients were defined as those aged ≥65 years with self-reported urge urinary incontinence (UUI) symptoms for ≥3 months, 2-15 UUI episodes/day, and at risk of deteriorating health by a score of ≥3 on the Vulnerable Elders Survey (VES)-13. Patients were evaluated for fesoterodine treatment response (defined as no UUI episodes) and persistence at weeks 12, 26, and 52. The model included a hypothetical health plan with 100,000 elderly members. A total of 7096 vulnerable elderly subjects were identified as the model target population based on the percentage of vulnerable elderly and annual prevalence of OAB among vulnerable elderly. OAB-related costs included fesoterodine drug acquisition costs, healthcare resource use (inpatient hospitalization, outpatient visits, and physician office visits), and OAB-related co-morbidities (falls/fractures, urinary tract infections, depression, and nursing home admissions). All costs were inflated to 2013 US$ using the medical care component of the consumer price index (CPI).When 7096 vulnerable elderly OAB patients were treated with fesoterodine, US healthcare payers could save $11,463,981 per year, or $1616 per patient vs no OAB pharmacotherapy. Univariate one-way sensitivity analyses supported the robustness of the findings and showed results were most sensitive to changes in fesoterodine efficacy followed by annual costs of inpatient hospitalization.From a US payer perspective, treating vulnerable elderly OAB patients with fesoterodine was cost-saving compared to no OAB pharmacotherapy.

Summary Aim: The aim of this study was to characterise the natural course of smoking cessation behaviour in a web-based survey of current and former cigarette smokers (CS and FS) in the United States. Methods: A web-based survey of CS and FS was conducted in April 2009; demographic and socioeconomic characteristics and smoking history (including the number of lifetime and length of latest quit attempts, aids used and time to relapse) were collated. The surveyed cohort was selected from prescreened CS and FS panellists and matched for age, race and education, to be representative of the US population. Descriptive statistics and time-to-event analyses using Kaplan–Meier curves were applied in the analysis of this report. Results: The final cohort comprised 512 CS and 566 FS (n = 1078). A larger proportion of FS than CS reported a longest smoke-free period of > 1 year (78.8% vs. 22.4%, respectively). As a greater variety of smoking cessation products became available over time, the proportion of unassisted quit attempts decreased from 76.1% prior to 1983 to 43.9% after 2006 for CS and from 79.3% to 50.3% for FS. The cumulative proportion of subjects relapsing was 31.3% by 1 week and 79.3% by 6 months. The estimated median time to next quit attempt was approximately 360 days. Conclusions: These data confirm that relapse is common and that as the variety of cessation modalities increase, the proportion of unassisted quit attempts decreases. Self-help or cold-turkey methods still provide significant alternatives even when pharmacotherapy is available. This study provides data related to the smoking history and smoking cessation patterns of a large, nationally representative sample of CS and FS.

The definitive version can be found at : http://onlinelibrary.wiley.com/ Copyright Wiley-Blackwell [Full text of this article is not available in the UHRA]

A fine-needle aspiration sample composed exclusively of Hurthle cells is interpreted as “suspicious for a follicular neoplasm, Hurthle cell type” (SFNHCT). Because some nonneoplastic Hurthle cell proliferations in Hashimoto thyroiditis (HT) mimic this cytologic pattern, we examined the positive predictive value (PPV) for malignancy of SFNHCT in patients with HT. Between 1992 and 2007, 401 patients with cytologic findings of SFNHCT were identified at 3 institutions. Histologic follow-up was available for 287 (71.6%), and malignancy was diagnosed in 69 (24.0%). Malignancy was present in 2 (PPV = 9.5%) of 21 patients with HT compared with 67 (PPV = 25.2%) of 266 patients without HT ( P = .081). Although the difference in the rate of malignancy between the HT and non-HT cohorts did not reach statistical significance, the lower risk of malignancy in the HT cohort more closely approximates the risk of cases interpreted as “atypia of undetermined significance.” For this reason, it might be appropriate for Hurthle cell–only aspirates from patients with HT to be categorized as either atypia of undetermined significance or SFNHCT.

To evaluate chronic obstructive pulmonary disease (COPD)-related expenditure and hospitalisation in COPD patients treated with tiotropium versus alternative long-acting bronchodilators (LABDs).Data were from the Thomson Reuters MarketScan Research Databases. COPD patients ≥ 35 years with at least one LABD claim between July 1, 2004 and June 30, 2006 were classified into five cohorts based on index LABD: monotherapy with tiotropium, salmeterol/fluticasone propionate, formoterol fumarate, or salmeterol or combination therapy. Demographic and clinical characteristics were evaluated for a 6-month pre-period and COPD-related utilisation and total costs were evaluated for a 12-month follow-up period. LABD relationship to COPD-related costs and hospitalisations were estimated by multivariate generalised linear modelling (GLM) and multivariate logistic regression, respectively.Of 52,274 patients, 53% (n = 27,457) were male, 71% (n = 37,271) were ≥ 65 years, and three LABD cohorts accounted for over 90% of the sample [53% (n = 27,654) salmeterol/fluticasone propionate, 23% (n = 11,762) tiotropium, and 15% (n = 7755) combination therapy]. Patients treated with salmeterol/fluticasone propionate (p0.001), formoterol fumarate (p = 0.032), salmeterol (p = 0.004), or with combination therapy (p0.001) had higher COPD-related costs and a greater risk of inpatient admission (p0.01 for all) versus tiotropium.These data are based on administrative claims and as such do not include clinical information or information on risk factors, like smoking status, that are relevant to this population.Patients treated with tiotropim had lower COPD-related expenditures and risk of hospitalisation than patients treated with other LABDs.

Lucas MA Goossens1, Christine L Baker2, Brigitta U Monz3, Kelly H Zou2, Maureen PMH Rutten-van Mölken11Institute for Medical Technology Assessment, Erasmus University, Rotterdam, The Netherlands; 2Pfizer Inc, New York City, NY, USA; 3Boehringer Ingelheim International GmbH, Ingelheim am Rhein, GermanyPurpose: When comparing chronic obstructive lung disease (COPD) interventions in database research, it is important to adjust for severity. Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines grade severity according to lung function. Most databases lack data on lung function. Previous database research has approximated COPD severity using demographics and healthcare utilization. This study aims to derive an algorithm for COPD severity using baseline data from a large respiratory trial (UPLIFT).Methods: Partial proportional odds logit models were developed for probabilities of being in GOLD stages II, III and IV. Concordance between predicted and observed stage was assessed using kappa-statistics. Models were estimated in a random selection of 2/3 of patients and validated in the remainder. The analysis was repeated in a subsample with a balanced distribution across severity stages. Univariate associations of COPD severity with the covariates were tested as well.Results: More severe COPD was associated with being male and younger, having quit smoking, lower BMI, osteoporosis, hospitalizations, using certain medications, and oxygen. After adjusting for these variables, co-morbidities, previous healthcare resource use (eg, emergency room, hospitalizations) and inhaled corticosteroids, xanthines, or mucolytics were no longer independently associated with COPD severity, although they were in univariate tests. The concordance was poor (kappa = 0.151) and only slightly better in the balanced sample (kappa = 0.215).Conclusion: COPD severity cannot be reliably predicted from demographics and healthcare use. This limitation should be considered when interpreting findings from database studies, and additional research should explore other methods to account for COPD severity.Keywords: GOLD, healthcare resource use, partial proportional odds logit

Aims To assess the prevalence of overactive bladder (OAB) among medically complex vulnerable elderly (MCVE) patients in the United States and to compare health status measures, functional status, healthcare events, use of healthcare services and costs between MCVE patients with and without OAB. Methods Using the 2001-2010 Medicare Current Beneficiary Surveys, we defined the MCVE as those respondents who were ≥65 years old with scores ≥3 on the Vulnerable Elders Survey-13. OAB diagnosis codes or self-reported use of antimuscarinic medications were used to identify MCVE individuals with OAB. Multiple regression analyses were used to estimate the adjusted relationship between OAB and the outcome measures. Results The annual prevalence of OAB among the MCVE increased from 9.6% in 2001 to 13.5% in 2010. MCVE individuals with OAB were more likely to have experienced falls or fractures (odds ratio [OR] = 1.6; 95% confidence interval [CI]: 1.3-2.0), urinary tract infections (OR = 4.3; 95% CI: 3.5-5.4), institutionalization (OR = 1.9; 95% CI: 1.4-2.5), limitations in activity of daily living (ADL) (OR = 1.4; 95% CI: 1.1-1.7) and instrumental ADL (OR = 1.5; 95% CI: 1.2-2.0), hospital admission (OR = 1.6; 95% CI: 1.3-2.0) and emergency department admissions (OR = 1.6; 95% CI: 1.3-2.0) than those without OAB. MCVE individuals with OAB incurred, on average, $7188 (2013 dollars) more in healthcare costs than those without OAB. Discussion/conclusions The prevalence of OAB in the MCVE population increased over time. OAB is associated with substantial clinical and economic burden. Further research is warranted to understand whether better management of the MCVE population with OAB may reduce healthcare resource use.

Introduction Men may choose to bypass the healthcare system to obtain a phosphodiesterase type 5 inhibitor (PDE5i). Aim Evaluate the characteristics and purchasing patterns of men obtaining a PDE5i without prior healthcare professional (HCP) interaction. Main Outcome Measures Prior HCP interaction, defined as having a prescription for any PDE5i, having a PDE5i sample from a physician, or buying the PDE5i in a retail pharmacy; and erectile dysfunction (ED, the Massachusetts Male Aging Study single-item question) were assessed. A multivariate regression analysis determined predictive factors for PDE5i purchase without prior HCP interaction. Methods A Web-based observational study was conducted in the United Kingdom, Germany, and Italy. Results Of the 11,899 participants, 1,252 (10.5% [95% CI, 10.0–11.1%]) reported PDE5i use in the last 6 months. PDE5is were obtained without prior HCP interaction by 403 users (32.3% [95% CI, 29.6–34.8%]); 65.5% of them had ED. Overall prevalence of men using PDE5is without HCP interaction was 3.0% (95% CI, 2.6–3.5%), 4.1% (95% CI, 3.5–4.6%), and 2.8% (95% CI, 2.1–3.5%) for men aged 18–34, 35–50, and >50 years, respectively (P = 0.0045). Predictive factors for obtaining a PDE5i without prior HCP interaction were embarrassment to speak to a physician (P = 0.0009) and the perception that this would be the cheapest way to get the medicine (P = 0.03). Conclusions Based on these findings, it can be estimated that approximately 6 million men in Europe might currently bypass the healthcare system to obtain a PDE5i. In addition to the risks associated with use of PDE5is from uncontrolled sources, because most of these men have ED, they also miss the opportunity for important health information or medical follow-up. HCPs should actively address ED and offer treatment to discourage men from seeking uncontrolled sources of ED medicines.

The objective of our study was to describe the T1 and T2 signal intensity characteristics of papillary renal cell carcinoma (RCC) and clear cell RCC with pathologic correlation.Of 539 RCCs, 49 tumors (21 papillary RCCs and 28 clear cell RCCs) in 45 patients were examined with MRI. Two radiologists retrospectively and independently assessed each tumor's T1 and T2 signal intensity qualitatively and quantitatively (i.e., the signal intensity [SI] ratio [tumor SI / renal cortex SI]). Of the 49 tumors, 37 (76%) were assessed for pathology features including tumor architecture and the presence of hemosiderin, ferritin, necrosis, and fibrosis. MRI findings and pathology features were correlated. Statistical methods included summary statistics and Wilcoxon's rank sum test for signal intensity, contingency tables for assessing reader agreement, concordance rate between the two readers with 95% CIs, and Fisher's exact test for independence, all stratified by RCC type.Papillary RCCs and clear cell RCCs had a similar appearance and signal intensity ratio on T1-weighted images. On T2-weighted images, most papillary RCCs were hypointense (reader 1, 13/21; reader 2, 14/21), with an average mean signal intensity ratio for both readers of 0.67 +/- 0.2, and none was hyperintense, whereas most clear cell RCCs were hyperintense (reader 1, 21/28; reader 2, 17/28), with an average mean signal intensity ratio for both readers of 1.41 +/- 0.4 (p0.05). A tumor T2 signal intensity ratio ofor = 0.66 had a specificity of 100% and sensitivity of 54% for papillary RCC. Most T2 hypointense tumors exhibited predominant papillary architecture; most T2 hyperintense tumors had a predominant nested architecture (p0.05).On T2-weighted images, most papillary RCCs are hypointense and clear cell RCCs, hyperintense. The T2 hypointense appearance of papillary RCCs correlated with a predominant papillary architecture at pathology.

While the use of p-values in evidence-based medicine (EBM) is consistent and well-defined, the application of statistical information in health law varies greatly. A comparative literature review of clinical and legal medical decision making using Medline (PubMed) and LexisNexis reveals large disparities in the mode and frequency with which statistical evidence is used in EBM when compared with health law. We present the historical background of the p-value in the statistical literature and legal case law, including several medical malpractice cases, and then compare the use of the p-value as statistical evidence in health law and clinical research. We suggest that health law may consider the establishment of statistical criteria for appropriate applications.

To prospectively determine in a fetal pig model whether diagnostic performance comparable to that of high-detail screen-film imaging can be achieved with computed radiography for the detection of simulated classic metaphyseal lesions (CMLs), by using Faxitron digital images as the reference standard, and whether radiation dose reduction is possible.This study was granted exempt status by the institutional review board and the animal care and use committee. Fractures simulating the CML were produced in distal femurs of 20 deceased fetal pigs. Twenty normal femurs served as control femurs. Femurs were imaged with a standard single-side-read 100-microm pixel sampling imaging plate (IP), a high-resolution dual-side-read 50-microm pixel sampling IP, and a high-detail screen-film imaging system. Eight tube current-time product settings (0.5-10.0 mAs) and two tube voltage selections (56 and 70 kVp) were employed. Two pediatric radiologists evaluated 920 images for fracture by using a five-point Likert scale. Area under the receiver operating characteristic curve (A(z)) values for the imaging systems were compared by using nonparametric chi(2) tests (all P.05).For pooled rater data, performance of computed radiography was comparable to that of screen-film imaging, and superior performance (P = .04) was achieved with the more experienced rater. The A(z) value tended to increase as the tube current-time product setting was increased. Within each system, there was no significant difference in A(z) values for all images obtained at 56 and 70 kVp (dual-side-read IP, P = .63; single-side-read IP, P = .25; screen-film imaging system, P = .5). At 56 kVp, a dose reduction of up to 69% was achieved, and accuracy of computed radiography was comparable to that of screen-film imaging.Findings in this study suggest that computed radiography can replace screen-film imaging in the detection of CMLs and may permit dose reduction.

The purpose of our study was to assess the utility of performing routine pelvic and lower extremity CT venography (CTV) along with pulmonary CT angiography (CTA) in all patients evaluated for pulmonary embolism.Eight hundred twenty-nine consecutive patients (281 men and 548 women) underwent CTA-CTV for pulmonary embolism. Reports were evaluated as follows: positive or negative for pulmonary embolism with or without deep venous thrombosis (DVT) or with nondiagnostic CTV. Coexisting factors of malignancy, previous venous thromboembolism (VTE), recent surgery, and cardiovascular disease comprised the high-risk group of 446 patients. The remaining 383 patients formed the low-risk group. Statistical analysis included four binary predictors (previous VTE, malignancy, cardiovascular disease, and surgery) and three binary outcome variables (pulmonary embolism, DVT, and VTE). Chi-square test and univariate and multivariate regression analyses were performed.VTE, pulmonary embolism, and DVT occurred in 152 (18.3%), 124 (15.0%), and 61 (7.3%) of 829 patients, respectively. Between the high-risk and low-risk groups, prevalence of VTE was 114 (25.6%) of 446 and 38 (9.9%) of 383 patients, respectively (p0.001); prevalence of pulmonary embolism was 92 (20.6%) of 446 and 32 (8.3%) of 383 patients, respectively (p0.001). Isolated DVT was found in 28 (3.4%) of 829 patients. The incremental value of CTV for the entire cohort was 3.4%, 0.72% in the low-risk group (six of 829) and 2.6% (22 of 829) in the high-risk group. For outcome variable VTE, malignancy and previous VTE were statistically significant (p = 0.04 and p0.001, respectively); for pulmonary embolism, malignancy and previous VTE were statistically significant (p = 0.03 and p = 0.005, respectively); for DVT, only previous VTE was statistically significant (p0.001).CTV should not be performed routinely in all patients evaluated for pulmonary embolism and may only be useful in patients with a high probability of pulmonary embolism, including those with a history of VTE and possible malignancy.

We reviewed our experience with 2 indicators of cytopathologist performance: the relative frequency of the interpretations atypical squamous cells of undetermined significance (ASC-US) and squamous intraepithelial lesion (SIL) and the frequency of positive test results for high-risk human papillomavirus (HR-HPV) DNA associated with a cytologic interpretation of ASC-US. Data derived for 9 cytopathologists were reviewed. ASC-US/SIL ranged from 0.99 to 4.02 (mean, 1.77) in 2005 and from 0.82 to 3.68 (mean, 1.81) in 2006. The HR-HPV+ rate for ASC-US ranged from 31.5% to 54.6% for individual cytopathologists (mean, 46.1%) in 2005 and from 29.6% to 61.8% (mean, 45.8%) in 2006. Combined data from both years showed only a slight negative correlation for these 2 variables. Both indicators together provide useful feedback to cytopathologists. We provide a working schema for interpreting perturbations in these indicators to assist in improving the quality of gynecologic cytology interpretations.

The aim of the study was to retrospectively determine the potential for radiation dose reduction at multidetector computed tomography (CT) of the paranasal sinus by using computer simulation of the effect of low–radiation dose acquisition on diagnostic image quality. This HIPAA compliant study was approved by the institutional human research committee. The need for informed patient consent was waived. Twenty patients underwent four-section CT at 120 kV, 170 mAs, and 4 × 1-mm collimation. Artificial image noise was added to the CT raw data by using a dedicated software platform. Acquisitions with effective tube currents of 134, 100, 67, and 33 mAs were simulated. Each raw data set was reconstructed with bone and soft-tissue algorithms, and two radiologists independently rated the images in blinded fashion. A two-sided paired Student t test was used for statistical analysis. The lowest radiation dose that still provided diagnostic quality was ≤67 effective mAs for osseous structures and ≤134 effective mAs f...